# Immune and metabolic correlates of Coccidioides disease spectrum and outcomes

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $374,579

## Abstract

Coccidioides infection leads to acute or chronic pulmonary disease (Valley Fever) with a wide spectrum
of disease severity. However, the mechanisms of coccidioidomycosis severity and therapeutic failures are not
fully elucidated and correlates of disseminated or unresolved infection are not well established. The overall
objective of Project 3 is to investigate the immune and metabolic correlates of Coccidioides infection and disease
spectrum and to identify mechanisms of disease pathogenesis. Our preliminary data of immune responses and
metabolomic profiles in samples from patients infected with Coccidioides identified the metabolic signature of
key dysregulated pathways. We hypothesize that Coccidioides infection-induced metabolic changes reflecting
the major dysregulated host cellular pathways can predict disease severity and clinical outcomes. We propose
to build on our collective strengths in coccidioidomycosis diagnostics and clinical care of large patient cohorts
with Coccidioides infection at UC Davis to determine the pathogenic mechanisms of coccidioidomycosis and to
investigate a prognostic biosignature that can identify the future course of disease progression. This project
leverages the availability of clinical sample collection from patients with coccidioidomycosis and database,
resources from the existing Centers, technical and scientific knowledge of immunological and metabolic
analyses, mouse models of coccidioidomycosis, strong preliminary data and a multi-disciplinary research team.
 There are three specific aims. Aim 1: To determine immune and metabolic correlates of the disease
spectrum and infection outcomes and identify pathways for therapeutic targeting. Longitudinal samples from
newly diagnosed patients with Coccidioides at UC Davis will be evaluated for immune and metabolic changes
and the key dysregulated cellular/metabolic pathways and correlates of disease outcomes will be identified. Aim
2: To identify immune and metabolic correlates of treatment failures and determine mechanisms contributing to
this treatment failure. Disseminated Coccidioides infection with severe disease is associated with
morbidity/mortality. Clinical samples from patients with disseminated Coccidioides receiving clinical care at UC
Davis will be enrolled in this prospective study. Aim 3: To investigate the pathogenic determinants of
Coccidioides that promote induction of immune and metabolic dysfunction and lung pathology in vivo. We will
utilize the mouse model of coccidioidomycosis to investigate the development of lung pathology, eosinophilia
and metabolic dysregulation by Coccidioides wild-type and mutant strains and map the pathogenic determinants.
An integrated analysis will be performed of host responses to Coccidioides in vivo through clinical (Project 3),
metabolic (Project 3) and transcriptomic (Project 2) data and to Coccidioides mutant strains in vitro and in the
mouse model (Core 3, Projects 1 and 2) Collectively, our proposed studies...

## Key facts

- **NIH application ID:** 10364969
- **Project number:** 1U19AI166798-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Satya Dandekar
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $374,579
- **Award type:** 1
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364969

## Citation

> US National Institutes of Health, RePORTER application 10364969, Immune and metabolic correlates of Coccidioides disease spectrum and outcomes (1U19AI166798-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10364969. Licensed CC0.

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